Biodistribution

To evaluate some of the health claims regarding octacosanol, researchers began to focus on the distribution of orally administered octacosanol throughout the body. Kabir and Kimura set out to further understand the mechanism of increased physical exercise and motor endurance by octacosanol.22 14C-labeled octacosanol administered to rats was found to primarily accumulate in adipose tissue, especially brown adipose tissue. Additionally, they found excretion through the feces to be very low, but present in measurable quantities in the urine and expired as 14CO2. This study suggests that a portion of 14C-octacosanol might be converted into fatty acids, which in turn supplies 14CO2 and energy through the process of ^-oxidation. There is, however, the possibility that all the free acid produced from octacosanol does not undergo direct oxidation and part of it is stored in the fat pool of the adipose tissue. Neptune et al. reported similar findings; the conversion of long-chain fatty acids to 14CO2 constituted only a small fraction of the total CO2 in the rat diaphragm.23

Kabir and Kimura further investigated the tissue distribution of 14C-octacosanol in liver and muscle of rats after a series of administrations.24 They found the highest amount of radioactivity in the liver (9.5% of administered dose), followed by the digestive tract (8.2% of administered dose) and the muscle (3.5% of administered dose). Interestingly enough, the radioactivity in the liver disappeared rapidly, while the muscle seemed to be able to store a considerable amount in response to the dose administered. More recently, Menendez et al. demonstrated that octacosanoic acid, as well as short-chain saturated and unsaturated fatty acids, are formed after an oral dosing of policosanol in rats and monkeys. These results reinforce the idea that octacosanol metabolism is linked to fatty acid metabolism via ^-oxidation.25

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